2-(3,4-diethoxyphenyl)-4-(2-carboxy-6-pyridyl)thiazole (or 6-[2-(3,4-diethoxyphenyl)thiazol-4-yl]pyridin-2-carboxylic acid) is a known compound. This compound is named as tetomilast. This tetomilast has active oxygen inhibitory action, cytokine generation inhibitory action, adhesion inhibitory action, etc., and it is useful for the treatment of ulcerative colitis, Crohn's disease, asthma, and the like (JP-A-5-51318 (paragraph [0015], Example 371) and JP-A-10-152437 (paragraphs [0024] and [0029]). In addition, tetomilast is also useful as a therapeutic agent for chronic obstructive pulmonary disease (JP-A-2003-104890). Moreover, such a tetomilast crystal is stable towards heat and moisture, and is excellent in terms of the disintegration property and dissolution property of tablets.
According to Example 371 of JP-A-5-51318, an anhydrous tetomilast crystal (hereinafter referred to as an “anhydrous tetomilast type B crystal”) is produced by allowing 3,4-diethoxythiobenzamide to react with 2-(2-chloroacetyl)-6-pyridine carboxylic acid and then recrystallizing the obtained tetomilast crude product from ethanol, for example.
Furthermore, according to Journal of Medicinal Chemistry, 1995, 38, pp. 353-358, such an anhydrous tetomilast type B crystal is produced by allowing 3,4-diethoxythiobenzamide to react with 2-(2-bromoacetyl)-6-pyridine carboxylic acid, then hydrolyzing the obtained methyl 6-[2-(3,4-diethoxyphenyl)thiazol-4-yl]pyridin-2-carboxylic acid methyl ester, and then recrystallizing the obtained tetomilast crude product from ethyl acetate.
However, since an anhydrous tetomilast type B crystal has the property of causing clogging, if such an anhydrous tetomilast type B crystal is produced by the conventional recrystallization method, an operating efficiency significantly deteriorates during filtration. Thus, it is difficult to produce anhydrous tetomilast type B crystals industrially in a large volume. Accordingly, it is strongly desired that a novel tetomilast crystal, which is advantageous in terms of industrial mass production, be developed.